Selenomethionine regulates cyclooxygenase-2 (COX-2) expression through nuclear factor-kappa B (NF-κB) in colon cancer cells

Durga P. Cherukuri, Anne Christine Goulet, Hiroyasu Inoue, Mark A. Nelson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Previously, we showed that selenomethionine (Se-Met) inhibits growth of colon cancer cells via suppressing COX-2 expression at both mRNA and protein level. However, the molecular mechanism by which Se-Met suppresses COX-2 expression remains to be elucidated. To this end, we transiently transfected HCA-7 cells with different COX-2 promoter constructs followed by Se-Met treatment (90 μM) for 12 h. The results suggested the role of nuclear factor-kappa B (NF-κB) in transcriptional regulation of COX-2. We also observed complete inhibition of DNA binding activity of NF-κB in Se-Met (90 μM) treated HCA-7 cells as shown by electrophoretic mobility shift assay (EMSA). Supershift assays with anti-p65 antibody identified p65 subunit in the protein complex. We further demonstrate dose-dependent inhibition of nuclear translocation of NF-κB/p65 in Se-Met treated HCA-7 cells, which could explain the observed reduction in DNA binding of NF-κB/p65. These results suggest that Se-Met regulates COX-2 at transcriptional level by modulating the activity of NF-κB transcription factor.

Original languageEnglish (US)
Pages (from-to)183-188
Number of pages6
JournalCancer Biology and Therapy
Volume4
Issue number2
StatePublished - Feb 2005

Keywords

  • COX-2
  • Colorectal cancer
  • NF-κB
  • Selenomethionine

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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